Application | Comment | Organism |
---|---|---|
drug development | the MetAP isozymes are potential targets to develop antitubercular therapeutics | Mycobacterium tuberculosis |
Cloned (Comment) | Organism |
---|---|
expression of the His-tagged isozyme MetAP1a as apoenzyme | Mycobacterium tuberculosis |
Inhibitors | Comment | Organism | Structure |
---|---|---|---|
3-[(4-fluorobenzyl)sulfanyl]-4H-1,2,4-triazole | - |
Mycobacterium tuberculosis | |
4-(2-methyl-1,3-thiazol-4-yl)benzene-1,2-diol | - |
Mycobacterium tuberculosis | |
4-(3-methylthiophen-2-yl)benzene-1,2-diol | - |
Mycobacterium tuberculosis | |
5-(2,5-dichlorophenyl)furan-2-carboxylic acid | - |
Mycobacterium tuberculosis | |
5-(2-chlorophenyl)furan-2-carboxylic acid | - |
Mycobacterium tuberculosis | |
5-[(2,4-dichlorobenzyl)sulfanyl]-4H-1,2,4-triazol-3-amine | - |
Mycobacterium tuberculosis | |
5-[(4-fluorobenzyl)sulfanyl]-4H-1,2,4-triazol-3-amine | - |
Mycobacterium tuberculosis | |
5-[(4-methylbenzyl)sulfanyl]-4H-1,2,4-triazol-3-amine | - |
Mycobacterium tuberculosis | |
additional information | a set of inhibitors displayed completely different inhibitory profiles on the two mycobacterial MetAPs in both potency and metalloform selectivity | Mycobacterium tuberculosis |
KM Value [mM] | KM Value Maximum [mM] | Substrate | Comment | Organism | Structure |
---|---|---|---|---|---|
0.011 | - |
L-methionine-4-methylcoumarin-7-amide | recombinant isozyme MetAP1a in presence of Ni2+ | Mycobacterium tuberculosis | |
0.082 | - |
L-methionine-4-methylcoumarin-7-amide | recombinant isozyme MetAP1a in presence of Co2+ | Mycobacterium tuberculosis | |
0.161 | - |
L-methionine-4-methylcoumarin-7-amide | recombinant isozyme MetAP1a in presence of Fe2+ | Mycobacterium tuberculosis | |
0.17 | - |
L-methionine-4-methylcoumarin-7-amide | recombinant isozyme MetAP1a in presence of Mn2+ | Mycobacterium tuberculosis |
Metals/Ions | Comment | Organism | Structure |
---|---|---|---|
Co2+ | activates, tight binding to the enzyme | Mycobacterium tuberculosis | |
Fe2+ | activates, tight binding to the enzyme | Mycobacterium tuberculosis | |
additional information | poor activation by Mn2+ | Mycobacterium tuberculosis | |
Ni2+ | most efficient activator, tight binding to the enzyme | Mycobacterium tuberculosis |
Organism | UniProt | Comment | Textmining |
---|---|---|---|
Mycobacterium tuberculosis | - |
two isozymes MtMetAP1a and MtMetAP1c | - |
Purification (Comment) | Organism |
---|---|
recombinant His-tagged isozyme MetAP1a in apoenzyme form | Mycobacterium tuberculosis |
Source Tissue | Comment | Organism | Textmining |
---|---|---|---|
additional information | the two MetAP isozymes, MtMetAP1a and MtMetAP1c, are expressed at different levels in growing and stationary phases | Mycobacterium tuberculosis | - |
Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
---|---|---|---|---|---|---|
L-methionine-4-methylcoumarin-7-amide + H2O | fluorogenic substrate | Mycobacterium tuberculosis | L-methionine + 7-amino-4-methylcoumarin | - |
? | |
additional information | MetAP carries out the cotranslational N-terminal methionine excision | Mycobacterium tuberculosis | ? | - |
? |
Subunits | Comment | Organism |
---|---|---|
More | differing active site structures of isozymes MetAP1a and MetAP1c | Mycobacterium tuberculosis |
Synonyms | Comment | Organism |
---|---|---|
MetAP | - |
Mycobacterium tuberculosis |
MetAP1a | - |
Mycobacterium tuberculosis |
methionine aminopeptidase | - |
Mycobacterium tuberculosis |
methionine aminopeptidase type 1a | - |
Mycobacterium tuberculosis |
More | MetAP belongs to the family of dinuclear metallohydrolases | Mycobacterium tuberculosis |
Turnover Number Minimum [1/s] | Turnover Number Maximum [1/s] | Substrate | Comment | Organism | Structure |
---|---|---|---|---|---|
0.014 | - |
L-methionine-4-methylcoumarin-7-amide | recombinant isozyme MetAP1a in presence of Fe2+ | Mycobacterium tuberculosis | |
0.045 | - |
L-methionine-4-methylcoumarin-7-amide | recombinant isozyme MetAP1a in presence of Ni2+ | Mycobacterium tuberculosis | |
0.07 | - |
L-methionine-4-methylcoumarin-7-amide | recombinant isozyme MetAP1a in presence of Mn2+ | Mycobacterium tuberculosis | |
0.36 | - |
L-methionine-4-methylcoumarin-7-amide | recombinant isozyme MetAP1a in presence of Co2+ | Mycobacterium tuberculosis |
IC50 Value | IC50 Value Maximum | Comment | Organism | Inhibitor | Structure |
---|---|---|---|---|---|
0.000031 | 0.0007 | recombinant isozyme MetAP1a in presence of different divalent metal ions, overview | Mycobacterium tuberculosis | 4-(2-methyl-1,3-thiazol-4-yl)benzene-1,2-diol | |
0.00007 | 0.0023 | recombinant isozyme MetAP1a in presence of different divalent metal ions, overview | Mycobacterium tuberculosis | 4-(3-methylthiophen-2-yl)benzene-1,2-diol | |
0.02 | 0.25 | recombinant isozyme MetAP1a in presence of different divalent metal ions, overview | Mycobacterium tuberculosis | 5-(2-chlorophenyl)furan-2-carboxylic acid | |
0.205 | 0.25 | and above, recombinant isozyme MetAP1a in presence of different divalent metal ions, overview | Mycobacterium tuberculosis | 5-[(2,4-dichlorobenzyl)sulfanyl]-4H-1,2,4-triazol-3-amine | |
0.25 | - |
above, recombinant isozyme MetAP1a in presence of different divalent metal ions, overview | Mycobacterium tuberculosis | 5-(2,5-dichlorophenyl)furan-2-carboxylic acid | |
0.25 | - |
above, recombinant isozyme MetAP1a in presence of different divalent metal ions, overview | Mycobacterium tuberculosis | 5-[(4-fluorobenzyl)sulfanyl]-4H-1,2,4-triazol-3-amine | |
0.25 | - |
above, recombinant isozyme MetAP1a in presence of different divalent metal ions, overview | Mycobacterium tuberculosis | 5-[(4-methylbenzyl)sulfanyl]-4H-1,2,4-triazol-3-amine | |
0.25 | - |
above, recombinant isozyme MetAP1a in presence of different divalent metal ions, overview | Mycobacterium tuberculosis | 3-[(4-fluorobenzyl)sulfanyl]-4H-1,2,4-triazole |
General Information | Comment | Organism |
---|---|---|
physiological function | MetAP is essential for bacterial survival | Mycobacterium tuberculosis |
kcat/KM Value [1/mMs-1] | kcat/KM Value Maximum [1/mMs-1] | Substrate | Comment | Organism | Structure |
---|---|---|---|---|---|
0.41 | - |
L-methionine-4-methylcoumarin-7-amide | recombinant isozyme MetAP1a in presence of Mn2+ | Mycobacterium tuberculosis | |
0.87 | - |
L-methionine-4-methylcoumarin-7-amide | recombinant isozyme MetAP1a in presence of Fe2+ | Mycobacterium tuberculosis | |
4.39 | - |
L-methionine-4-methylcoumarin-7-amide | recombinant isozyme MetAP1a in presence of Co2+ | Mycobacterium tuberculosis | |
40.91 | - |
L-methionine-4-methylcoumarin-7-amide | recombinant isozyme MetAP1a in presence of Ni2+ | Mycobacterium tuberculosis |